Recent studies in this and other laboratories have shown that 13C, 31P, and 1H nuclear magnetic resonance (nmr) studies of short (100-200 nucleotide pairs-np) double stranded DNA molecules are practical. We propose multi-nuclear (principally 13C), multi-field nmr studies of DNA conformational dynamics and interactions with model carcinogens, toxins and drugs. The overall objective is to relate the conformational dynamics of DNA to normal and aberrant DNA functions in vivo. Specific objectives are (i) to describe the chemical shift environments for base and sugar carbons; (ii) to elucidate overall and internal DNA motional dynamics using multi-field 13C and 31p nmr data (linewidths, T1s, NOEs) coupled with current theory of relaxation effects of ionic strength and bulk solvent changes on the conformational dynamics of specific DNA sites, (iv) to assess the usefulness of these nmr methods for investigating mechanisms of interaction of small molecules with DNA, and (v) to study in depth those DNA-small molecule interactions judged most amenable to nmr analysis. 13C, and in some cases 31p and 1H nmr spectra will be obtained at high and moderate fields using special optimized probes on three Fourier transform superconducting nmr spectrometers. Relatively homogenous length, double stranded DNA subfractions spanning a range from 50-300 np will be prepared from native chromatin digested with micrococcal nuclease, followed by gel filtration. Small molecules chosen for study include intercalating agents (proflavine, ethidium, quinacrine, actinomycin D; a steroid diamine (dipyrandium); alkylating agents potentially useful as reporter groups; and heavy metals (Hg++ and Ag+). 199Hg and other metal nuclide nmr will be used to supplement 13C, 31P, and 1H data in metal binding studies.